Antineoplastic Chemotherapy Protocols

Systemic chemotherapy must start within 28 days of randomisation. In the control arm, systematic chemotherapy with OxMdG consists of oxaliplatin (85 mg/m² infusion over 2 hours), folinic acid (l-folinic acid 175 mg or d, l-folinic acid 350 mg infusion over 2 hours) and 5-FU (400 mg/m² bolus followed by a 2400 mg/m² continuous infusion over 46 hours). This cycle is then repeated every 14 days for 12 cycles. In the treatment arm, SIRT is administered on the third or fourth day of the second chemotherapy cycle. In addition, the same chemotherapy regimen is used except in cycles 2–4 when the oxaliplatin dose was reduced to 60 mg/m² as this has been demonstrated as the maximum tolerated dose in an earlier phase I-II trial [11 (link)]. SIRT requires a hepatic arteriogram and a liver-to-lung breakthrough nuclear medicine scan to ensure suitability for receiving this procedure, and to plan the delivery of the SIR-spheres. A separate SIR-Spheres users’ manual details the technique for delivery of the SIR-Spheres. The prescribed activity of SIR-Spheres will be determined from the patient’s body surface area (BSA), the percentage tumour involvement, and the magnitude of liver-to-lung shunting. The dosing charts used are consistent with a similar contemporary study (SIRFLOX study protocol, submitted to BMC Cancer, March 2014).
The use of a licensed biological agent (e.g. cetuximab, bevacizumab) is permitted in this trial at the discretion of the treating investigator and at doses determined by local practice, but the intention to treat a patient with a biological agent should be declared at the time of randomisation. Intention to treat with a biological agent is a stratification factor in the trial. The biological agent can be added at any time during protocol chemotherapy for patients randomised to chemotherapy only, but, on account of a potential interaction with liver radiotherapy, it should not be delivered prior to cycle 7 for patients randomised to receive SIRT.
Once protocol treatment is completed, patients should be given the best available care based upon clinical assessment and patient preference. In both arms, if following treatment response the patient is deemed a candidate for surgical resection (assessed at 3 and 6 months after starting protocol treatment), and the patient undergoes surgical resection and/or complete ablation of their primary and metastatic cancer, protocol OxMdG chemotherapy should be continued as scheduled if appropriate.

We retrospectively enrolled 278 patients diagnosed with advanced NSCLC who regularly received DP (docetaxel plus cisplatin), GP (gemcitabine plus cisplatin), NP (vinorelbine plus cisplatin), PC (pemetrexed plus cisplatin) and TP (paclitaxel plus cisplatin) chemotherapy regimens at the Affiliated Hospital of Xu Zhou Medical University from January May 2012 and July 2020.
The inclusion criteria were as follows: (1) NSCLC was pathologically diagnosed; (2) NSCLC was stage III or IV according to the American Joint Committee on Cancer (AJCC) 8th edition; (3) the patient received chemotherapy for more than two cycles without a combination of targeted therapy, radiation therapy and immune therapy; (4) the patient had no other cancer history and laboratory test results were obtained before treatment.
The exclusion criteria were as follows: (1) patients with missing or incomplete data; (2) patients who underwent surgery, radiotherapy, immunotherapy before standard chemotherapy protocols, (3) patients who had obvious fever and pneumonia before chemotherapy.
This retrospective study was approved by the ethics committee of the Affiliated Hospital of Xu Zhou Medical University.

The patients responded to a structured questionnaire prepared by the researchers to evaluate clinical and sociodemographic conditions and habits such as smoking, alcoholism, and oral hygiene. This questionnaire was applied by the researchers. In addition, patients' medical records were analyzed to collect information related to general health, pre-existing pathologies, medications used, tumor staging and location, and RT and chemotherapy protocols used.

Patient population and data collection
In this multicenter, retrospective cohort study, patients aged 65 years or older, diagnosed with extensive-stage SCLC between January 2009 and December 2021 in the Medical Oncology Departments of the University of Health Sciences Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Türkiye, and Gazi University School Medicine, Ankara, Türkiye, were included. Patients who were under 65 years of age at the time of diagnosis and did not develop progression after curative treatment and patients with a second malignancy were excluded from the study.
The baseline demographic characteristics of the patients (gender, age at diagnosis, and smoking status), clinicopathological data (Eastern Cooperative Oncology Group (ECOG) performance status (PS)), and tumor characteristics (stage and metastasis sites), treatment characteristics (palliative chemotherapy options, number of chemotherapy cycles, and treatment responses), laboratory findings (lactate dehydrogenase-LDH), disease progression, and survival data were examined and transferred to the database. American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th Edition, was used for disease staging.
The two chemotherapy protocols given to the patients included in the study were as follows: (i) a combination of cisplatin and etoposide (cisplatin 80 mg/m²/day IV on day 1, etoposide 100 mg/m²/day IV on days 1-3), or (ii) a combination of carboplatin and etoposide (carboplatin area under the curve 5 (AUC5) IV on day 1, etoposide 100 mg/m²/day IV on days 1-3). Both regimens were given up to six cycles.
Response to chemotherapy was defined according to response evaluation in solid tumors criteria 1.1 (RECIST 1.1). Complete response (CR) was defined as the disappearance of all target lesions, the short axis of all pathological lymph nodes <10 mm; partial response (PR) was defined as a reduction of at least 30% in the sum of the diameters of the target lesions; progressive disease (PD) was defined as the appearance of one or more new lesions or the size of the target lesions increasing by 20% of the sum of the long diameters; and stable disease (SD) was defined as neither sufficient reduction to be considered as PR nor sufficient increase to be considered as PD.
Statistical analysis
IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States) was used for data analysis. Progression-free survival (PFS) was defined as the time from the beginning of chemotherapy treatment to disease progression or death, and overall survival (OS) was defined as the time from the date of extensive-stage diagnosis to death. Survival analyses were performed by the Kaplan-Meier method and subgroups were compared by log-rank test. Factors that may be related to PFS and OS were investigated by univariate analysis. Factors that showed significant association with survival were evaluated by multivariate Cox regression analysis. P<0.05 was considered statistically significant.
Ethical approval
Ethical approval was obtained from the Ethics Committee of the University of Health Sciences, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital (approval number: 2022-04/1798,20.04.2022). Our study complies with the principles of the Helsinki Declaration.